〔Abstract〕 Objective To observe the effect of Yiqi Fuzheng Yangyin Huatan prescription combined with tyrosine kinase inhibitors (TKIs) on delaying TKIs resistance and quality of life of patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer in stage Ⅲa ~ Ⅳ. Methods A retrospective analysis was performed on 80 patients diagnosed with stage Ⅲa ~ Ⅳ EGFR mutant non-small cell lung cancer in Quanzhou Hospital of Traditional Chinese Medicine from January 2016 to January 2019, who were divided into a control group and an observation group according to different treatment regimen, with 40 cases in each group. Patients in the control group were treated with EGFR-TKIs alone, and patients in the observation group were treated with Yiqi Fuzheng Yangyin Huatan prescription on the basis of the control group. The quality of life, safety, short-term efficacy and time of disease progression of patients in the two groups were recorded. Results After treatment, the quality of life in the observation group was significantly better than that in the control group, and the difference was statistically significant (P < 0.05). No rash and diarrhea above grade Ⅲ occurred in the two groups during treatment. The incidence of rash in the observation group was 75.00 % (30/40), which was not statistically significant compared with 77.50 % in the control group (P > 0.05). The incidence of diarrhea in the observation group was 52.5 %, which was not statistically significant compared with 55.00 % in the control group (P > 0.05). The disease control rate (DCR) of the observation group was 82.50 %, higher than that of the control group (70.00 %), and the difference was statistically significant (P < 0.05). The median time to disease progression was 11.5 months in the control group, 15.0 months in the observation group, and 3.5 months of delayed TKIs resistance. Logrank test showed that the difference was statistically significant (P < 0.05). Conclusion Yiqi Fuzheng Yangyin Huatan prescription combined with TKIs in the treatment of stage Ⅲa ~ Ⅳ EGFR mutant non-small cell lung cancer can significantly improve the quality of life of patients, delay drug resistance and improve survival benefits.